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Increased Substance P Responses in Dorsal Root Ganglia and Intestinal Macrophages during Clostridium difficile Toxin A Enteritis in Rats

Castagliuolo, Ignazio ; Keates, Andrew C. ; Qiu, Bosheng ; Kelly, Ciaran P. ; Nikulasson, Sigfus ; Leeman, Susan E. ; Pothoulakis, Charalabos

Proceedings of the National Academy of Sciences - PNAS, 1997-04, Vol.94 (9), p.4788-4793 [Periódico revisado por pares]

United States: National Academy of Sciences of the United States of America

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Título:
Increased Substance P Responses in Dorsal Root Ganglia and Intestinal Macrophages during Clostridium difficile Toxin A Enteritis in Rats
Autor: Castagliuolo, Ignazio ; Keates, Andrew C. ; Qiu, Bosheng ; Kelly, Ciaran P. ; Nikulasson, Sigfus ; Leeman, Susan E. ; Pothoulakis, Charalabos
Assuntos: Animals ; Bacterial Toxins - pharmacology ; Biological Sciences ; Biphenyl Compounds - pharmacology ; Clostridioides difficile ; Control loops ; Digestive system ; Enteritis ; Enterotoxins - pharmacology ; Epithelial cells ; Ganglia, Spinal - metabolism ; Gastroenterology ; Ileitis - metabolism ; Inflammation ; Intestinal Mucosa - metabolism ; Lumbosacral Region ; Macrophage Activation ; Macrophages ; Macrophages - metabolism ; Male ; Messenger RNA ; Mucosa ; Nervous system ; Neurons ; Peptides ; Rats ; Rats, Wistar ; RNA, Messenger - analysis ; Rodents ; Secretion ; Substance P - antagonists & inhibitors ; Substance P - biosynthesis ; Substance P - genetics ; Toxins ; Tumor Necrosis Factor-alpha - metabolism
É parte de: Proceedings of the National Academy of Sciences - PNAS, 1997-04, Vol.94 (9), p.4788-4793
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
Susan E. Leeman
To whom reprint requests should be addressed at: Division of Gastroenterology, Dana 501, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215.
Descrição: Previously we reported that pretreatment of rats with the substance P (SP) antagonist CP-96,345 inhibits the enterotoxic responses following administration of toxin A from Clostridium difficile into ileal loops, indicating that SP participates in the intestinal responses to this toxin. We now report that injection of toxin A into rat ileum causes a rapid increase in SP content in lumbar dorsal root ganglia (DRG) and mucosal scrapings 30-60 min after toxin A administration. Toxin A-mediated fluid secretion, mannitol permeability, and ileal histologic damage is significantly increased only after 2 hr. Toxin A also causes an increase in the abundance of SP mRNA in lumbar DRG and ileal mucosa as measured by reverse transcription-PCR. Lamina propria macrophages (LPMs) obtained from toxin A-injected loops release greater amounts of tumor necrosis factor α (TNFα ) and SP as compared with LPMs isolated from buffer-injected loops (P < 0.01). Pretreatment of rats with the SP antagonist CP-96,345 inhibits toxin A-mediated TNFα release from isolated LPMs, whereas an inactive enantiomer (CP-96,344) of the SP antagonist has no effect. LPMs obtained from toxin A-injected ileal loops incubated in vitro with SP (10-8to 10-9M) show enhanced TNFα secretion, whereas LPMs isolated from buffer-injected loops do not respond to SP. In addition, LPMs obtained from toxin A-injected ileal loops incubated in vitro with CP-96,345 showed a diminished TNFα release. Our results indicate that activated LPMs secrete SP during toxin A enteritis that can lead to secretion of cytokines, suggesting an autocrine/paracrine regulation of cytokine secretion by SP from LPMs during intestinal inflammation.
Editor: United States: National Academy of Sciences of the United States of America
Idioma: Inglês

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Increased Substance P Responses in Dorsal Root Ganglia and Intestinal Macrophages during Clostridium difficile Toxin A Enteritis in Rats

Castagliuolo, Ignazio ; Keates, Andrew C. ; Qiu, Bosheng ; Kelly, Ciaran P. ; Nikulasson, Sigfus ; Leeman, Susan E. ; Pothoulakis, Charalabos

United States: National Academy of Sciences of the United States of America

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